This is an application for support for an ongoing program devoted to final events in atherosclerosis, that is rupture of the atherosclerotic plaque. The hypothesis explored is that macrophage death plays a critical role in progression of the lesion. To test this hypothesis, we propose a combination of an in vitro assay designed to identify genes controlling macrophage death and an animal model already demonstrated to show spontaneous plaque rupture. Work done under this program has the potential to identify novel therapeutic approaches to dealing with the progression from existing atherosclerotic lesions to atherosclerotic lesions that become clinically significant.